Cholesterol drug raises doubts
Study reveals bempedoic acid has a modest rate of success
Millions of Americans who are at risk for heart attacks and whose LDL cholesterol levels are disturbingly high have been told over and over again by their doctors to take a statin. But many people cannot or will not take the drugs, often reporting that statins make their muscles ache.
Statins, cheap generic drugs, have been shown repeatedly to slash cholesterol levels and prevent heart attacks, strokes and deaths.
Now, a study with 14,000 patients of a drug that lowers LDL levels and was designed to avoid muscle aches was found to modestly reduce the risk of heart attacks, strokes and other complications from heart disease.
The study was published Saturday in The New England Journal of Medicine and presented at the annual meeting of the American College of Cardiology. The medication joins several statin alternatives that have been shown to reduce cardiac illnesses, but some experts say they doubt the drug is any more likely to be embraced by patients who are wary of statins and, often, other LDL-lowering drugs.
The drug, bempedoic acid, is not new. The Food and Drug Administration approved it three years ago because it lowers LDL levels, but “it was not used a lot,” said Dr. John Alexander, a cardiologist at Duke, who was not associated with the study. He wrote an accompanying editorial in the journal. The reason, he said, is that while earlier research showed that while the drug lowered LDL cholesterol, no studies showed that it actually reduced a patient’s chances of a heart attack or a stroke or death from heart disease.
Because there was no outcome data, insurers generally have not covered its cost of about $140 a month.
“In cardiology and cardiovascular disease prevention, we expect outcome data,” Alexander said.
The new study showed that bempedoic acid modestly decreased the combined risk of cardiovascular complications — heart attacks, strokes, blocked arteries that needed to be reopened with stents or bypass surgery or cardiovascular death — although it did not decrease the overall mortality rate.
The trial was directed by Dr. Steven Nissen of the Cleveland Clinic and was paid for by the drug’s maker, Esperion Therapeutics, which sells it under the brand name Nexletol.
It involved people who were at high risk for a heart attack or stroke and randomly assigned to take bempedoic acid or a placebo. Their average LDL level was 139 mg per deciliter. Cardiologists generally say such patients should get their LDL below 70.
The participants had to sign a statement saying: “I can’t tolerate these medications (called statins) even though I know they would reduce my risk of a heart attack or stroke or death. My doctor has explained and I am aware that many patients who are unable to tolerate a single statin medication may also be able to tolerate a different statin or dose.”
Bempedoic acid reduced LDL levels by about 20%, not enough to get patients to the goal level. At the end of the study, the average LDL level in those taking the drug was 107, compared with 136 in the patients taking a placebo. In contrast, statins can reduce LDL levels by as much as 50%.
After just a bit more than 1½ years, 819, or 11.7%, of patients in the bempedoic acid group had one of the heart-related complications.
In the placebo group, 927 patients, or 13.3%, had such an event.
Participants did not have muscle aches or an increased risk of diabetes, the most common complaints with statins. With bempedoic acid, a small percentage in the trial experienced an increased risk of gout, an inflammation of the joints that is treatable, and increased risk of gallstones.
Now the question is, how important is this drug going to be?
Bempedoic acid is the sixth cholesterol-lowering drug, in addition to statins, that has been demonstrated to reduce heart attacks and strokes, noted Dr. Michael Davidson, director of the lipid clinic at the University of Chicago Pritzker School of Medicine who founded a company, New Amsterdam Pharma, that is developing an LDL-lowering drug.
The others are bile acid resins, niacin, ezetimibe, PCSK9 inhibitors and CETPi. They have varying effects on LDL and range from cheap to expensive. With this array of drugs, Davidson said he hoped doctors could start focusing on getting high-risk patients’ LDL levels as low as possible, whatever it takes.
Dr. Harlan Krumholz, a Yale cardiologist, said given bempedoic acid’s modest effects and the fact that other drugs also lower LDL, it “is unlikely to be a game-changer.”
Dr. Benjamin Ansell, a lipid expert at UCLA, said the drug was “better than nothing” but that “it isn’t enough” for people who have high LDL levels and are at high risk.